The one-carbon metabolism as an underlying pathway for placental DNA methylation – a systematic review

<p>Epigenetic modifications, including DNA methylation, are proposed mechanisms explaining the impact of parental exposures to foetal development and lifelong health. Micronutrients including folate, choline, and vitamin B₁₂ provide methyl groups for the one-carbon metabolism and subsequent DNA methylation processes. Placental DNA methylation changes in response to one-carbon moieties hold potential targets to improve obstetrical care. We conducted a systematic review on the associations between one-carbon metabolism and human placental DNA methylation. We included 22 studies. Findings from clinical studies with minimal ErasmusAGE quality score 5/10 (<i>n</i> = 15) and <i>in vitro</i> studies (<i>n</i> = 3) are summarized for different one-carbon moieties. Next, results are discussed per study approach: (1) global DNA methylation (<i>n</i> = 9), (2) genome-wide analyses (<i>n</i> = 4), and (3) gene specific (<i>n</i> = 14). Generally, one-carbon moieties were not associated with global methylation, although conflicting outcomes were reported specifically for choline. Using genome-wide approaches, few differentially methylated sites associated with S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), or dietary patterns. Most studies taking a gene-specific approach indicated site-specific relationships depending on studied moiety and genomic region, specifically in genes involved in growth and development including <i>LEP</i>, <i>NR3C1, CRH</i>, and <i>PlGF</i>; however, overlap between studies was low. Therefore, we recommend to further investigate the impact of an optimized one-carbon metabolism on DNA methylation and lifelong health.</p>